High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness

Abstract

Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti‐PS100, anti‐SOX10, anti‐CD10, and anti‐TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow‐up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs.

Circulating tumor microemboli (CTM) and vimentin+ circulating tumor cells (CTCs) detected by a size-based platform predict worse prognosis in advanced colorectal cancer patients during chemotherapy

“…Moreover, CTM was captured by this size-based platform, and CTM-positive patients with advanced CRC had worse survival than isolated CTCs-positive patients. It was reported that tumor cells within CTM could be protected from anoikis and were relatively resistant to cytotoxic drugs [35], and CTM was an independent prognostic factor [35, 36]. Hence, CTM would be more malignant and aggressive than isolated CTCs.…”

Technical Insights into Highly Sensitive Isolation and Molecular Characterization of Fixed and Live Circulating Tumor Cells for Early Detection of Tumor Invasion

“…According to cytopathological criteria [16, 30, 111], cancer cells from patients are usually larger than 16 microns. The presence in blood of intact cancer cells smaller than 8 microns, i.e.…”

“…Such cancer cells are expected to be of clinical interest [2, 4] as shown by independent clinical studies using ISET ® [3, 17, 18, 22, 24, 26, 35, 103, 111–115] (Reviewed in Table H in S1 File). …”

“…Cancer cells isolated by ISET ® have been studied across various cancer types and stages, as well as in patients at risk of developing cancer [10–12, 16–27, 29–32, 35, 97, 103, 104, 108, 111–119] (Reviewed in Table I in S1 File). The global number of CCC and CCM has been reported to be higher in patients with advanced disease.…”

Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective

“…neutral endopeptidase and/or neprilysin), and legumain (EC 3.4.22.34; syn. asparaginyl endopeptidase) (33)(34)(35)(36). However, on the basis of only few current data, their usefulness as biomarkers still is difficult to estimate.…”